The NONO::TFE3 fusion has been described in MiT family translocation renal cell carcinomas as well as extracutaneous perivascular epithelioid cell tumors (PEComas). PEComas are known to express myogenic and melanocytic markers but SOX10 and p63 positivity has never been reported. We report two primary cutaneous tumors that morphologically and molecularly fit PEComas, both harboring the NONO::TFE3 fusion, but with an unusual immunophenotype of SOX10 and p63 positivity. One case was on an 80-year-old male\'s finger, and the other one was on a 72-year-old female\'s thigh. Both were well-circumscribed multinodular dermal tumors composed of nests of monotonous epithelioid to spindled cells with pale to vacuolated cytoplasm, some of which were arranged around blood vessels. Both tumors were positive for SOX10, S100, and p63, focally positive for Melan-A, and negative for myogenic markers. There are very little data regarding the molecular findings of primary cutaneous PEComas. While the NONO::TFE3 fusion has been identified in extracutaneous PEComas, it has never been reported in primary cutaneous cases. We believe these cases represent a previously undescribed subtype of cutaneous tumor which shows some immunophenotypic expression of melanocytic markers and we named these cases NONO::TFE3 fusion cutaneous epithelioid and spindle cell tumor. Further, we raise the question of whether this tumor should fall under the rubric of PEComa because of its morphology, partial expression of melanocytic markers, and the presence of the NONO::TFE3 fusion, or whether these tumors represent a separate novel class of tumors since the immunophenotypic expression of SOX10 and p63 is unusual for PEComas.

Malignant peripheral nerve sheath tumors (MPNSTs) usually arise in the soft tissues. Intraosseous MPNSTs are rare. They may arise de novo but are typically associated with neurofibromatosis type 1 (NF1) and radiation therapy. Our patient is a 58-year-old female patient that presented with right shoulder pain. An MRI showed a shoulder mass, and percutaneous bone biopsy demonstrated morphology suggestive of an MPNST; besides, on immunohistochemistry, SOX10 was positive, and H3K27me3 expression was entirely lost. The patient underwent total resection of the right proximal humerus and endoprosthetic shoulder reconstruction, followed by radiation therapy and chemotherapy. Only a few cases in the mandible, spine, maxilla, ulna, metacarpal, tarsal, and one in the humerus have been published. In this paper, we contribute with an additional case of primary intraosseous MPNST in the humerus and a brief literature review.

BACKGROUND: Recent studies report that cerebellar glioblastoma (GBM) is categorized into the RTK1 methylation class. GBM pediatric RTK (pedRTK) subtypes are distinct from those of adult GBM. We present a unique adult case of cerebellar GBM classified into the pedRTK subtype.
METHODS: Magnetic resonance imaging revealed a homogeneous enhancing lesion in the right cerebellum in a 56-year-old woman presenting with ataxia and dizziness. Arterial spin labeling and angiographic findings and the intraoperative orange-colored tumor appearance were reminiscent of hemangioblastoma. She showed an atypical presentation in terms of high glucose metabolism. The histological diagnosis was high-grade glioma with differentiation similar to central nervous system neuroblastoma. The methylation class was GBM pedRTK1. Consistent with this classification, immunoexpression was positive for SOX10 and negative for ANKRD55. She underwent craniospinal radiotherapy (23.4 Gy) with a boost to the tumor bed (total 55.8 Gy). Twelve courses of temozolomide therapy were administered. There was no recurrence 18 months after surgery.
CONCLUSIONS: Radiological and intraoperative findings, such as hemangioblastoma and high glucose metabolism, were notable characteristics in the present case. Both glial and neuronal differentiation and SOX10 immunoexpression were presenting pathological features. Similar cerebellar GBMs might form a previously unestablished subtype. Establishing effective molecular diagnoses is important.

Background: Waardenburg syndrome (WS) is a rare genetic disorder characterized by congenital sensorineural hearing loss and pigmentary abnormalities of the hair, skin and eyes. However, exotropia is rarely reported. The purpose of this study is to describe the clinical characteristics of three sporadic patients with WS and congenital exotropia and to investigate the disease-causing genes for them. Methods: Patients underwent detailed physical and ocular examinations. Ocular alignment and binocular status were evaluated. DNA was extracted and whole exome sequencing was performed to detect the pathogenic variations in the disease-causing genes for WS. Cloning sequencing was carried out for those indel variations. Results: Three unrelated patients were diagnosed with Waardenburg syndrome and congenital exotropia. Four novel variants, including c.136delA (p.I46Sfs*64) and c.668G>T (p.R223L) in PAX3, c.709dupC (p.Q237Pfs*119) in COL11A2, c.426G>A (p.W142X) in SOX10 gene, were detected in this study. Conclusion: Simultaneous presence of congenital exotropia and WS in our patients is suggested that WS could be involved in malfunction in the multiple nerve systems. Our genetic study will expand the mutation spectrum of PAX3, COL11A2 and SOX10 genes, and is helpful for further study on the molecular pathogenesis of WS.

BACKGROUND: Esophageal schwannomas originating from Schwann cells are extremely rare esophageal tumors. They commonly occur in the upper and middle esophagus but less frequently in the lower esophagus. Herein, we report a rare case of a large lower esophageal schwannoma misdiagnosed as a leiomyoma. We also present a brief literature review on lower esophageal schwannomas.
METHODS: A 62-year-old man presented with severe dysphagia lasting 6 mo. A barium esophagogram showed that the lower esophagus was compressed within approximately 5.5 cm. Endoscopy revealed the presence of a large submucosal protuberant lesion in the esophagus at a distance of 32-38 cm from the incisors. Endoscopic ultrasound findings demonstrated a 4.5 cm × 5.0 cm hypoechoic lesion. Chest computed tomography revealed a mass of size approximately 53 mm × 39 mm × 50 mm. Initial tests revealed features indicative of leiomyoma. After multidisciplinary discussions, the patient underwent a video-assisted thoracoscopic partial esophagectomy. Further investigation involving immunohistochemical examination confirming palisading spindle cells as positive for S100 and Sox10 led to the final diagnosis of a lower esophageal schwannoma. There was no tumor recurrence or metastasis during follow-up.
CONCLUSIONS: The final diagnosis of esophageal schwannoma requires histopathological and immunohistochemical examination. The early appropriate surgery favors a remarkable prognosis.

BACKGROUND: Hereditary motor and sensory neuropathy, also referred to as Charcot-Marie-Tooth disease (CMT), is most often caused by a duplication of the peripheral myelin protein 22 (PMP22) gene. This duplication causes CMT type 1A (CMT1A). CMT1A rarely occurs in combination with other hereditary neuromuscular disorders. However, such rare genetic coincidences produce a severe phenotype and have been reported in terms of \"double trouble\" overlapping syndrome. Waardenburg syndrome (WS) is the most common form of a hereditary syndromic deafness. It is primarily characterized by pigmentation anomalies and classified into four major phenotypes. A mutation in the SRY sex determining region Y-box 10 (SOX10) gene causes WS type 2 or 4 and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, WS, and Hirschsprung disease. We describe a 11-year-old boy with extreme hypertrophic neuropathy because of a combination of CMT1A and WS type 2. This is the first published case on the co-occurrence of CMT1A and WS type 2.
METHODS: The 11-year-old boy presented with motor developmental delay and a deterioration in unstable walking at 6 years of age. In addition, he had congenital hearing loss and heterochromia iridis. The neurological examination revealed weakness in the distal limbs with pes cavus. He was diagnosed with CMT1A by the fluorescence in situ hybridization method. His paternal pedigree had a history of CMT1A. However, no family member had congenital hearing loss. His clinical manifestation was apparently severe than those of his relatives with CMT1A. In addition, a whole-body magnetic resonance neurography revealed an extreme enlargement of his systemic cranial and spinal nerves. Subsequently, a genetic analysis revealed a heterozygous frameshift mutation c.876delT (p.F292Lfs*19) in the SOX10 gene. He was eventually diagnosed with WS type 2.
CONCLUSIONS: We described a patient with a genetically confirmed overlapping diagnoses of CMT1A and WS type 2. The double trouble with the genes created a significant impact on the peripheral nerves system. Severe phenotype in the proband can be attributed to the cumulative effect of mutations in both PMP22 and SOX10 genes, responsible for demyelinating neuropathy.

Waardenburg syndrome (WS) is a rare genetic disorder. The purpose of this study was to investigate clinical and molecular characteristics of WS in four probands from four different Iranian families.
The first patient was a 1-year-old symptomatic boy with congenital hearing loss and heterochromia iridis with a blue segment in his left iris. The second case was a 1.5-year-old symptomatic girl who manifested congenital profound hearing loss, brilliant blue eyes, and skin hypopigmentation on the abdominal region at birth time. The third patient was an 8-month-old symptomatic boy with developmental delay, mild atrophy, hypotonia, brilliant blue eyes, skin hypopigmentation on her hand and foot, Hirschsprung disease, and congenital profound hearing loss; the fourth patient was a 4-year-old symptomatic boy who showed dystopia canthorum, broad nasal root, synophrys, skin hypopigmentation on her hand and abdomen, brilliant blue eyes, and congenital profound hearing loss. Whole exome sequencing (WES) was used for each proband to identify the underlying genetic factor. Sanger sequencing was performed for validation of the identified mutations in probands and the available family members. A novel heterozygous frameshift mutation, c.996delT (p.K334Sfs*15), on exon 8 of the MITF gene was identified in the patient of the first family diagnosed with WS2A. Two novel de novo heterozygous mutations including a missense mutation, c.950G > A (p.R317K), on exon 8 of the MITF gene, and a frameshift mutation, c.684delC (p.E229Sfs*57), on the exon 3 of the SOX10 gene were detected in patients of the second and third families with WS2A and PCWH (Peripheral demyelinating neuropathy, Central dysmyelinating leukodystrophy, Waardenburg syndrome, Hirschsprung disease), respectively. A previously reported heterozygous frameshift mutation, c.1024_1040del AGCACGATTCCTTCCAA, (p.S342Pfs*62), on exon 7 of the PAX3 gene was identified in the patient of the fourth family with WS1.
An exact description of the mutations responsible for WS provides useful information to explain the molecular cause of clinical features of WS and contributes to better genetic counseling of WS patients and their families.

Primary multiple obturator nerve schwannomas originate from Schwann cells and are extremely rare. Patients with schwannomas are asymptomatic and a retroperitoneal schwannoma is often misdiagnosed as an adnexal mass. In the present study, we describe a 58-year-old woman in whom a right adnexal mass accompanied by endometrial polyp was found incidentally through transvaginal ultrasound. The mass was diagnosed as multiple obturator nerve schwannomas after laparoscopy. Immunohistochemical assay confirmed the schwannomas to be positive for SOX10. To our knowledge, this is the first report to demonstrate a case of multiple schwannomas originating from the obturator nerve and treated by laparoscopic resection.

Primary cutaneous Ewing sarcoma is a very rare entity with less than 100 cases reported in the literature, sharing the same morphological and immunohistochemical characteristics as their osseous counterparts. Herein, to the best of our knowledge, we report the first case in English literature of a molecularly confirmed Ewing sarcoma with diffuse and strong SOX10 immunoreactivity. This exceedingly rare immunohistochemical finding along with the rarity of this tumor could easily lead to a misdiagnosis with significant repercussions. Our case highlights the difficulty in diagnosing primary cutaneous Ewing sarcoma as well as the pivotal role molecular diagnostics can play in specific scenarios.

We herein report a patient who was diagnosed as having olfactory groove schwannoma (OGS) which was negative for CD57 (Leu7) but positive for Schwann/2E and Sox10. A 13-year-old female with a chief complaint of headache was referred to our department due to a tumor lesion in the anterior skull base identified by magnetic resonance imaging (MRI). At the first visit, she did not exhibit altered consciousness, motor palsy, anosmia, seizures, or café au lait spots. On contrast-enhanced computed tomography (CT), a heterogeneously enhanced tumor, 50 × 45 × 50 mm in size, was observed at the anterior skull base. The left cribriform plate was thinner on bone window CT. The tumor exhibited strong, heterogeneous gadolinium enhancement on MRI as well. Slight tumor staining was observed by angiography of the left internal carotid artery but not the left external carotid artery. The patient was preoperatively diagnosed as having meningioma and underwent gross tumor resection via the basal interhemispheric approach. The tumor was strongly positive for S-100 protein and negative for epithelial membrane antigen and CD57 by immunostaining. The tumor was positive for both Schwann/2E and Sox10, which aided in the differential diagnosis between OGSs and olfactory ensheathing cell (OEC) tumors, and the definitive diagnosis was OGS. The assessment of immunoreactivities for Schwann/2E and Sox10 might be necessary to differentiate CD57-negative Schwannomas from OEC tumors.